PILOT AND EXPLORATORY STUDIES CORE - SUMMARY Within the context of the OAIC's overall mission, the Pilot and Exploratory Studies Core (PESC) aims to provide catalytic support ? seed funding, core support, and mentorship - for innovative pilot research projects that generate data on the mechanisms of FPT action to facilitate more definitive mechanistic studies, feasibility data to guide efficacy trials, hypothesis generating or proof-of-concept exploratory studies and retrospective analysis of existing epidemiologic data that inform FPT interventions. The aims of this PESC are: Aim 1. To build a translational pipeline for early stage innovative and interdisciplinary research by providing funding and infrastructure for: ? Generation of proof-of-concept preclinical data to expedite the development of FPTs. ? Mechanistic studies for target identification or hypotheses building by which FPTs exert their effects on skeletal muscle and physical function (e.g., PES-1). ? Pilot testing of translational interventions or research protocols in human subjects or animal models for safety, feasibility, or determination of optimal time course or dosage (e.g., PES-2, PES-3). Aim 2: To build connectivity between PESC investigators and OAIC core resources. Aim 3: To monitor biannually and guide success of research projects by PESC investigators. Aim 4. To catalyze pilot and exploratory projects into high quality peer-reviewed publications, grant applications, and intellectual property/ patents, whenever possible. We selected 3 innovative studies for PESC support, from among a pool of 11 applications, because these studies are well aligned with the OAIC's mission of promoting the development of FPTs: PES-1 will characterize microRNAs in exercise and as biomarkers for anabolic response in aged adults. PES-2 will evaluate whether a home-based exercise program can improve functional outcomes in patients undergoing trans-catheter aortic valve replacement. PES-3 willl determine if transcranial brain stimulation can improve physical function in older adults. During its initial 5 years of funding, Boston OAIC supported 11 PES projects from 1 to 2.5 years. A $750,000 OAIC investment yielded $17.95 million in extramural funding, two patents, and 75 peer reviewed publications including papers in Aging Cell (Guo 2013, Jasuja 2014), a book on translational biology in medicine (Montano 2014, Elsevier Publishers), PNAS (Hettmer 2011), Circulation (Jefferson 2010) and NEJM (Basaria 2012). This PESC will be led by two scientists with complementary expertise and mentoring skills; Dr. Monty Montano, a translational scientist with expertise in muscle and aging; and, Dr. Douglas Kiel, a clinical investigator with expertise in musculoskeletal decline with aging and intervention trials of function promoting therapies.